TWI610912B - Method for producing 2-chloromethylbenzaldehyde, 2-chloromethylbenzaldehyde-containing composition, and method for storing same - Google Patents
Method for producing 2-chloromethylbenzaldehyde, 2-chloromethylbenzaldehyde-containing composition, and method for storing same Download PDFInfo
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Abstract
本發明提供以高收率得到產業上有用的含2-氯甲基苯甲醛之液組成物的製造方法。詳細地，提供一種2-氯甲基苯甲醛之製造方法，其具有：混合1-二氯甲基-2-氯甲基苯與84.5重量%以上的濃度之硫酸之步驟(A)；及，混合步驟(A)所得的混合物與水之步驟(B)。 The present invention provides a method for producing a commercially useful liquid composition containing 2-chloromethylbenzaldehyde in high yield. Specifically, a method for producing 2-chloromethylbenzaldehyde having a step (A) of mixing 1-dichloromethyl-2-chloromethylbenzene with sulfuric acid having a concentration of 84.5 wt% or more; The step (B) of mixing the mixture obtained in the step (A) with water.
Description
本發明關於2-氯甲基苯甲醛之製造方法、含2-氯甲基苯甲醛之組成物及其保管方法。 The present invention relates to a method for producing 2-chloromethylbenzaldehyde, a composition containing 2-chloromethylbenzaldehyde, and a method for storing the same.
2-氯甲基苯甲醛(以下亦記載為2CMAD)係適用作為醫藥及電子材料的中間體(專利文獻1~3)。然而，關於其具體的製法、物性等，並沒有進行詳細的揭示。 2-Chloromethylbenzaldehyde (hereinafter also referred to as 2CMAD) is suitable as an intermediate for pharmaceuticals and electronic materials (Patent Documents 1 to 3). However, detailed descriptions of its specific methods, physical properties, and the like have not been made.
唯一係在專利文獻1中有藉由1-二氯甲基-2-氯甲基苯(以下亦記載為TCOX)之水解，可製造2CMAD之記載，但其詳細的水解條件係不清楚。 The only one disclosed in Patent Document 1 is hydrolysis of 1-dichloromethyl-2-chloromethylbenzene (hereinafter also referred to as TCOX), and 2CMAD can be produced. However, the detailed hydrolysis conditions are not clear.
[專利文獻1]特開2006-335737號公報 [Patent Document 1] JP-A-2006-335737
[專利文獻2]特開平6-016685號公報 [Patent Document 2] JP-A-6-016685
[專利文獻3]特開昭62-051641號公報 [Patent Document 3] JP-A-62-051641
本發明者們參考類似化合物之水解條件，詳細地檢討，結果發現即使依照上述專利文獻1記載的方案，使TCOX與水反應，僅那樣子也無法收率良好地得到 2CMAD，確認有應應對的技術問題。又，已知如此所得之2CMAD係在室溫下的安定性未必可充分滿足者，在以其作為原料的反應中，安定性亦未必可充分滿足者。即使在專利文獻1~3之實施例中藉由實驗室的小規模、短時間反應，以中程度的收率得到目的物，但在設想工業規模的大量合成之情況中，若收率降低或其目的物在保管中分解，則難以作為工業原料使用。 The inventors of the present invention have conducted a detailed review with reference to the hydrolysis conditions of the similar compounds. As a result, it has been found that TCOX can be reacted with water according to the embodiment described in Patent Document 1, and it is not possible to obtain a good yield in such a manner. 2CMAD, confirm that there are technical problems that should be addressed. Further, it is known that the stability of 2CMAD obtained in this manner at room temperature is not necessarily sufficient, and stability in the reaction using the 2CMAD as a raw material may not be sufficiently satisfied. Even in the examples of Patent Documents 1 to 3, the target product is obtained in a medium-scale yield by a small-scale, short-time reaction in a laboratory, but in the case of envisioning a large-scale synthesis on an industrial scale, if the yield is lowered or When the object is decomposed during storage, it is difficult to use it as an industrial material.
本發明者們專心致力地檢討，而達成本發明。即，本發明係如以下。 The present inventors have devoted themselves to reviewing and achieving the present invention. That is, the present invention is as follows.
[1]一種2-氯甲基苯甲醛之製造方法，其特徵為具有：混合1-二氯甲基-2-氯甲基苯與84.5重量%以上的濃度之硫酸之步驟(A)；及混合步驟(A)所得的混合物與水之步驟(B)。 [1] A method for producing 2-chloromethylbenzaldehyde, which comprises the step (A) of mixing sulfuric acid having a concentration of 1-dichloromethyl-2-chloromethylbenzene and a concentration of 84.5 wt% or more; The step (B) of mixing the mixture obtained in the step (A) with water.
[2]如[1]記載之製造方法，其中具有中和前述步驟(B)所得的混合物之有機相之步驟。 [2] The production method according to [1], which has a step of neutralizing the organic phase of the mixture obtained in the above step (B).
[3]如[1]或[2]記載之製造方法，其中更具有混合所得的2-氯甲基苯甲醛與選自由聚合抑制劑及抗氧化劑所成之群組中的至少一種之步驟。 [3] The production method according to [1] or [2], wherein the step of mixing at least one of 2-chloromethylbenzaldehyde and at least one selected from the group consisting of a polymerization inhibitor and an antioxidant is further included.
[4]如[3]記載之製造方法，其中前述選自由聚合抑制劑及抗氧化劑所成之群組中的至少一種，係選自由2,6-雙(1,1-二甲基乙基)-4-甲基苯酚(BHT)、氫醌、單甲 基氫醌及硫代二苯胺所成之群組中的至少一種。 [4] The production method according to [3], wherein the at least one selected from the group consisting of a polymerization inhibitor and an antioxidant is selected from 2,6-bis(1,1-dimethylethyl). )-4-methylphenol (BHT), hydroquinone, monomethyl At least one of the group consisting of hydrazine and thiodiphenylamine.
[5]如[1]~[4]中任一項記載之製造方法，其中步驟(A)中之84.5重量%以上的濃度之硫酸，係相對於1-二氯甲基-2-氯甲基苯1莫耳而言，含有0.4莫耳以上之水。 [5] The production method according to any one of [1] to [4] wherein the sulfuric acid having a concentration of 84.5 wt% or more in the step (A) is relative to 1-dichloromethyl-2-chloromethyl In the case of benzene 1 mole, it contains more than 0.4 moles of water.
[6]一種組成物，其特徵為含有2-氯甲基苯甲醛與選自由聚合抑制劑及抗氧化劑所成之群組中的至少一種。 [6] A composition comprising 2-chloromethylbenzaldehyde and at least one selected from the group consisting of a polymerization inhibitor and an antioxidant.
[7]如[6]記載之組成物，其中前述選自由聚合抑制劑及抗氧化劑所成之群組中的至少一種，係選自由2,6-雙(1,1-二甲基乙基)-4-甲基苯酚(BHT)、氫醌、單甲基氫醌及硫代二苯胺所成之群組中的至少一種。 [7] The composition according to [6], wherein the at least one selected from the group consisting of a polymerization inhibitor and an antioxidant is selected from the group consisting of 2,6-bis(1,1-dimethylethyl) At least one of the group consisting of -4-methylphenol (BHT), hydroquinone, monomethylhydroquinone, and thiodiphenylamine.
[8]如[6]或[7]記載之組成物，其中更含有1-二氯甲基-2-氯甲基苯，以與1-二氯甲基-2-氯甲基苯的莫耳量[MTCOX]之關係所規定之2-氯甲基苯甲醛的莫耳量[M2CMAD]之含有比率([η2CMAD]=[M2CMAD]/([M2CMAD]+[MTCOX]))為95%以上。 [8] The composition according to [6] or [7], which further contains 1-dichloromethyl-2-chloromethylbenzene, and is the same as 1-dichloromethyl-2-chloromethylbenzene molar amount of 2-chloro-methylbenzaldehyde the predetermined amount of the ear [M TCOX] the relationship between [M 2CMAD] the content ratio ([η 2CMAD] = [M 2CMAD] / ([M 2CMAD] + [M TCOX] )) is more than 95%.
[9]一種組成物之保管方法，其係在氮氣環境下保管[6]~[8]中任一項之組成物。 [9] A method for storing a composition, which comprises storing the composition according to any one of [6] to [8] in a nitrogen atmosphere.
依照本發明之製造方法，即使在工業的規模的實施中，也可以優異的收率來製造2-氯甲基苯甲醛。再者，依照本發明，可提供安定性優異之含2-氯甲基苯甲醛的組成物及其保管方法。 According to the production method of the present invention, 2-chloromethylbenzaldehyde can be produced in an excellent yield even in an industrial scale. Further, according to the present invention, a composition containing 2-chloromethylbenzaldehyde excellent in stability and a method for storing the same can be provided.
以下，對於本發明，以其較佳的實施態樣為基礎來詳細說明。 Hereinafter, the present invention will be described in detail based on preferred embodiments thereof.
本實施態樣中的2-氯甲基苯甲醛(2CMAD)之製造方法之特徵為：混合1-二氯甲基-2-氯甲基苯(TCOX)與84.5重量%以上之硫酸之步驟(A)；及混合步驟(A)所得之混合物與水之步驟(B)。藉由進行步驟(A)及步驟(B)，TCOX係以高轉化率轉換成2CMAD。以下，將TCOX轉換成2CMAD之反應記載為「水解反應」或「水解」。 The method for producing 2-chloromethylbenzaldehyde (2CMAD) in the present embodiment is characterized by the step of mixing 1-dichloromethyl-2-chloromethylbenzene (TCOX) with sulfuric acid of 84.5 wt% or more ( A); and the step (B) of mixing the mixture obtained in the step (A) with water. By carrying out step (A) and step (B), TCOX is converted to 2CMAD with high conversion. Hereinafter, the reaction in which TCOX is converted into 2CMAD is described as "hydrolysis reaction" or "hydrolysis".
步驟(A)所用之硫酸係H2SO4的水溶液，其濃度為84.5重量%以上，較佳為96重量%以下。硫酸濃度更佳為85%重量以上，尤佳為90重量%以上。相對於TCOX1莫耳而言，硫酸之量較佳為1莫耳以上，更佳為2莫耳以上。硫酸之量係沒有上限，但相對於TCOX 1莫耳而言，4莫耳以下係符合實際。相對於TCOX 1莫耳而言，硫酸量若為1莫耳以上，則為了完成TCOX與84.5重量%以上的硫酸之反應，不會過度花費時間而較佳。 The aqueous solution of the sulfuric acid-based H 2 SO 4 used in the step (A) has a concentration of 84.5 wt% or more, preferably 96 wt% or less. The sulfuric acid concentration is more preferably 85% by weight or more, and particularly preferably 90% by weight or more. The amount of sulfuric acid is preferably 1 mole or more, more preferably 2 moles or more, relative to TCOX1 mole. There is no upper limit to the amount of sulfuric acid, but it is practical to be 4 moles or less relative to TCOX 1 mole. When the amount of sulfuric acid is 1 mol or more with respect to TCOX 1 mole, it is preferable to carry out the reaction of TCOX with 84.5 wt% or more of sulfuric acid without excessively taking time.
步驟(A)中的反應溫度係沒有特別的限定，以15℃以上的溫度可充分維持反應之速度而較佳。在所生成的2CMAD之安定性之點，此反應溫度較佳為25℃以下。反 應時間係沒有特別的限制，但在工業的生產中若考慮現實的範圍，則較佳為15小時以下，更佳為8小時以下。下限值係沒有特定，但3小時以上係符合實際。 The reaction temperature in the step (A) is not particularly limited, and it is preferred to sufficiently maintain the reaction rate at a temperature of 15 ° C or higher. At the point of stability of the generated 2CMAD, the reaction temperature is preferably 25 ° C or less. anti- The time is not particularly limited, but in consideration of the actual range in industrial production, it is preferably 15 hours or shorter, more preferably 8 hours or shorter. The lower limit is not specific, but it is more than 3 hours.
實施步驟(A)的方法係沒有限制，通常藉由在上述濃度的硫酸中滴下1-二氯甲基-2-氯甲基苯之方法來進行。又，從在反應初期見到誘導期來看，亦可採用滴下1-二氯甲基-2-氯甲基苯的一部分，確認TCOX與84.5重量%以上的硫酸之反應開始後，添加剩餘的1-二氯甲基-2-氯甲基苯之方法。硫酸濃度若比84.5重量%還低，則反應不完成。原料中所用的1-二氯甲基-2-氯甲基苯，例如可蒸餾鄰二甲苯之經由光氯化所製造者而使用。 The method for carrying out the step (A) is not limited, and is usually carried out by dropping 1-dichloromethyl-2-chloromethylbenzene in the above-mentioned concentration of sulfuric acid. Further, from the viewpoint of the induction period at the initial stage of the reaction, a part of 1-dichloromethyl-2-chloromethylbenzene may be dropped, and after the reaction of TCOX with 84.5 wt% or more of sulfuric acid is started, the remaining portion may be added. Method of 1-dichloromethyl-2-chloromethylbenzene. If the sulfuric acid concentration is lower than 84.5 wt%, the reaction is not completed. The 1-dichloromethyl-2-chloromethylbenzene used in the raw material is used, for example, by distillation of ortho-xylene by photochlorination.
於本實施態樣中，步驟(A)中所用之硫酸，即使相對於TCOX 1莫耳而言，含有未達1莫耳的水時，也可在後述的步驟(B)中，藉由混合步驟(A)所得的混合物與水，而完成水解反應。即，水解反應係可在步驟(A)中進行，也可經由步驟(B)完成。步驟(A)中所用之硫酸，相對於TCOX 1莫耳而言，較佳為含有0.4莫耳以上的水，更佳為含有0.8莫耳以上的水，尤更佳含有1莫耳以上的水。硫酸中所含有的水量之上限係沒有特定，但相對於TCOX 1莫耳而言，2莫耳以下係符合實際。 In the present embodiment, the sulfuric acid used in the step (A) may be mixed in the step (B) described later even if it contains water of less than 1 mol with respect to the TCOX 1 molar. The mixture obtained in the step (A) is combined with water to complete the hydrolysis reaction. That is, the hydrolysis reaction can be carried out in the step (A) or via the step (B). The sulfuric acid used in the step (A) preferably contains water of 0.4 mol or more, more preferably contains 0.8 mol or more of water, more preferably contains 1 mol or more of water, relative to the TCOX 1 molar. . The upper limit of the amount of water contained in the sulfuric acid is not specific, but it is practically equivalent to 2 moles or less relative to the TCOX 1 mole.
步驟(A)所得之混合物係在反應液內以均勻混合的狀態存在，但藉由進行混合該混合物與水之步驟(B)，可得到2CMAD，而且可分離取得含2CMAD的有機化合物成分，分離該有機化合物成分與水及其中所溶解的成分。 此處，於前述有機化合物成分中，原料化合物的1-二氯甲基-2-氯甲基苯(TCOX)與生成物的2-氯甲基苯甲醛(2CMAD)會共存。兩有機化合物成分之分離通常不容易，由於2CMAD為容易分解之化合物，故進行藉由加熱的精製處理等係不符合實際。換言之，於上述2CMAD的生成反應之階段中，以高收率取得2CMAD者係極重要。 The mixture obtained in the step (A) is present in a state of being uniformly mixed in the reaction liquid, but by carrying out the step (B) of mixing the mixture with water, 2CMAD can be obtained, and the organic compound component containing 2CMAD can be separated and separated. The organic compound component is combined with water and a component dissolved therein. Here, among the organic compound components, 1-dichloromethyl-2-chloromethylbenzene (TCOX) as a raw material compound and 2-chloromethylbenzaldehyde (2CMAD) as a product are present. Separation of the two organic compound components is generally not easy, and since 2CMAD is a compound which is easily decomposed, it is not practical to carry out purification treatment by heating or the like. In other words, in the stage of the formation reaction of the above 2CMAD, it is extremely important to obtain 2CMAD in a high yield.
於本發明中，所謂的「水」只要沒有特別預先指明，則使用包含水及水性介質(水可溶的物質溶解在水中之水溶液)之定義。 In the present invention, the term "water" is defined as a water-containing medium and an aqueous medium (an aqueous solution in which a water-soluble substance is dissolved in water) unless otherwise specified.
步驟(B)所使用的水之量，以硫酸濃度成為70重量%以下之方式添加者，在良好地進行分液，分離出2CMAD之點為較佳。水的使用量係沒有上限，但若超出需要地使用，則經濟性變不利。添加水的溫度，係考慮生成物的安定性，較佳為在30℃以下進行，但若考慮水的凝固點，則在5℃以上30℃以下之間，較低的溫度為更佳。於硫酸濃度成為70重量%以下，將有機層與水層分液時之溫度，從分液性之點來看，較佳為在15℃~30℃進行。 The amount of water used in the step (B) is preferably such that the sulfuric acid concentration is 70% by weight or less, and it is preferable to carry out liquid separation well and separate 2CMAD. There is no upper limit on the amount of water used, but if it is used more than necessary, the economy becomes unfavorable. The temperature at which the water is added is preferably 30 ° C or lower in consideration of the stability of the product. However, in consideration of the freezing point of water, the temperature is preferably between 5 ° C and 30 ° C, and a lower temperature is more preferable. When the sulfuric acid concentration is 70% by weight or less, the temperature at which the organic layer and the aqueous layer are separated from each other is preferably from 15 ° C to 30 ° C from the viewpoint of liquid separation.
如上述，以高收率所得之2CMAD，係意味原料化合物的TCOX少。依照本實施形態，由於2CMAD的收率高，在後續所欲的化學製品之合成中，可提供高濃度的2CMAD。於本實施形態中，較佳為提高此2CMAD濃度[η2CMAD]，即相對於TCOX的莫耳量[MTCOX]與2CMAD的莫耳量[M2CMAD]之總量而言2CMAD之莫耳量[M2CMAD]的比率[η2CMAD]=[M2CMAD]/([M2CMAD]+[MTCOX])。較佳為 使2CMAD濃度[η2CMAD]成為95%以上，更佳成為98%以上。上限係沒有特定，例如若考慮延長反應時間，則規定為100%以下者亦可能。如此地，由於得到高濃度的2CMAD，可成為將TCOX壓制在少量之良質原料，藉由後述的安定化可進一步發揮其優點。2CMAD的濃度較佳為95%以上，在95~99%的範圍經安定化者為更佳。 As described above, 2CMAD obtained in a high yield means that the TCOX of the starting compound is small. According to this embodiment, since the yield of 2CMAD is high, a high concentration of 2CMAD can be provided in the synthesis of a subsequent desired chemical. In the present embodiment, it is preferred to increase the 2CMAD concentration [η 2CMAD ], that is, the molar amount of 2CMAD relative to the total amount of TCOX molar amount [M TCOX ] and 2CMAD molar amount [M 2CMAD ]. The ratio of [M 2CMAD ] [η 2CMAD ] = [M 2CMAD ] / ([M 2CMAD ] + [M TCOX ]). Preferably, the 2CMAD concentration [η 2CMAD ] is 95% or more, and more preferably 98% or more. The upper limit is not specific. For example, if it is considered to extend the reaction time, it is also possible to set it to 100% or less. As described above, since a high concentration of 2CMAD is obtained, it is possible to suppress TCOX to a small amount of a good raw material, and the stability can be further enhanced by the stabilization described later. The concentration of 2CMAD is preferably 95% or more, and it is more preferably stabilized in the range of 95 to 99%.
如上述，於上述第1實施態樣中，較佳為藉由進行步驟(A)及步驟(B)，分離成有機相與水相之二層。此時，進行分液操作，通常水洗所分離取得的有機相，但其溶液(有機相)的pH係顯示強酸性，耐不住長期的保存。此係因為2-氯甲基苯甲醛非常容易受到氧化，於酸性條件下容易變化成酞內酯。此為工業上難以大量處理2-氯甲基苯甲醛者。本發明者們發現，藉由進行混合2-氯甲基苯甲醛與選自由聚合抑制劑及抗氧化劑所成之群組中的至少一種(以下亦記載為安定劑)之步驟，而提高2-氯甲基苯甲醛之安定性。藉此，通常的製造日程(例如2日左右)之2-氯甲基苯甲醛的保管係成為可能，可大量地使用作為下一步驟之原料。作為安定劑，例如可舉出2,6-雙(1,1-二甲基乙基)-4-甲基苯酚(以下亦記載為BHT)、氫醌、單甲基氫醌、硫代二苯胺、甲醇、Quino Power(註冊商標)、MnCl2、CuCl2、TEMPO等，較佳係選自由2,6-雙(1,1-二甲基乙基)-4-甲基苯酚(BHT)、 氫醌、單甲基氫醌及硫代二苯胺所成之群組中的至少一種，更佳為硫代二苯胺、BHT，尤佳為BHT。安定劑的使用量，相對於2CMAD而言以重量基準表示，較佳為50~500ppm(安定劑/2CMAD)，更佳為使用100~200ppm。其使用量比50ppm少時或比500ppm還多時，2-氯甲基苯甲醛之安定性，與不和安定劑混合的2CMAD之安定性相比，會不升高。特別地由於過度許多的添加反而引起雜質的增加，故較佳為不使成為該量。 As described above, in the first embodiment described above, it is preferred to separate the two layers of the organic phase and the aqueous phase by performing the steps (A) and (B). At this time, the liquid separation operation is carried out, and the organic phase obtained by separation is usually washed with water, but the pH of the solution (organic phase) shows strong acidity and cannot withstand long-term storage. This is because 2-chloromethylbenzaldehyde is very susceptible to oxidation and readily changes to azlactone under acidic conditions. This is industrially difficult to treat 2-chloromethylbenzaldehyde in large quantities. The present inventors have found that 2-step 2-methylchlorobenzaldehyde is added to a step selected from at least one selected from the group consisting of a polymerization inhibitor and an antioxidant (hereinafter also referred to as a stabilizer). The stability of chloromethylbenzaldehyde. In this way, it is possible to store 2-chloromethylbenzaldehyde in a usual manufacturing schedule (for example, about 2 days), and it is possible to use a large amount of the raw material as the next step. Examples of the stabilizer include 2,6-bis(1,1-dimethylethyl)-4-methylphenol (hereinafter also referred to as BHT), hydroquinone, monomethylhydroquinone, and thiodi Aniline, methanol, Quino Power (registered trademark), MnCl 2 , CuCl 2 , TEMPO, etc., are preferably selected from 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT). And at least one selected from the group consisting of hydroquinone, monomethylhydroquinone and thiodiphenylamine, more preferably thiodiphenylamine, BHT, and particularly preferably BHT. The amount of the stabilizer used is expressed on a weight basis with respect to 2CMAD, preferably 50 to 500 ppm (stabilizer/2CMAD), more preferably 100 to 200 ppm. When the amount used is less than 50 ppm or more than 500 ppm, the stability of 2-chloromethylbenzaldehyde does not increase as compared with the stability of 2CMAD which is not mixed with the stabilizer. In particular, since excessive addition causes an increase in impurities, it is preferable not to make this amount.
已觀測到2CMAD之自分解反應係經由空氣中的氧之氧化而生成酞內酯。因此，較佳為在氮氣環境下保管、反應。 It has been observed that the self-decomposition reaction of 2CMAD produces an azlactone via oxidation of oxygen in the air. Therefore, it is preferred to store and react in a nitrogen atmosphere.
說明本發明的第3實施態樣之將含有2CMAD的混合液予以中和而安定化之處理。具體地，可舉出藉由將經過步驟(A)及步驟(B)所得之含有2CMAD的混合液與鹼性水溶液(較佳為含有鹼緩衝劑的水溶液)予以混合而中和之操作。此時，較佳為測定含有2CMAD的有機相及水相之混合液的pH，調整至pH6~8。 A third embodiment of the present invention will be described in which a mixed solution containing 2CMAD is neutralized and stabilized. Specifically, an operation of neutralizing a mixed solution containing 2CMAD obtained in the steps (A) and (B) with an aqueous alkaline solution (preferably an aqueous solution containing an alkali buffer) may be mentioned. In this case, it is preferred to measure the pH of the mixed solution of the organic phase and the aqueous phase containing 2CMAD to adjust to pH 6-8.
此時添加於水中的鹼之種類係沒有限制，但較佳為磷酸氫二鈉。磷酸氫二鈉具有緩衝效果，即使使用量稍微變化，也可保持pH。若使用氫氧化鈉水溶液等之鹼，藉由與2CMAD之混合而將其液嚴密地管理在pH6~8者，係需要相當勞力，較佳為使用如上述之具有緩衝效果的調整 劑。再者，藉由添加上述所示的安定劑，可進一步提高長期保存性。再者，於本發明中，所謂的pH，只要沒有特別預先指明，則指藉由實施例所示的方法測定之值。 The type of the base added to the water at this time is not limited, but is preferably disodium hydrogen phosphate. Disodium hydrogen phosphate has a buffering effect, and the pH can be maintained even if the amount used is slightly changed. If a base such as an aqueous solution of sodium hydroxide is used, and the liquid is closely managed at a pH of 6 to 8 by mixing with 2CMAD, it requires a considerable amount of labor, and it is preferable to use an adjustment having a buffering effect as described above. Agent. Further, by adding the stabilizer described above, the long-term storage stability can be further improved. Further, in the present invention, the pH is a value measured by the method shown in the examples unless otherwise specified.
如上述，依照本發明的較佳實施態樣，將1-二氯甲基-2-氯甲基苯(TCOX)在室溫下水解，而收率、純度皆良好地轉換成2-氯甲基苯甲醛(2CMAD)(第1實施態樣)。此時所生成的2-氯甲基苯甲醛之濃度[η2CMAD]之較佳範圍係如先前所述。再者，依照上述第2實施態樣及第3實施態樣，2-氯甲基苯甲醛係即使在通常的生產日程(例如2日左右)之保存中也不分解，可供應給下一步驟之反應。 As described above, according to a preferred embodiment of the present invention, 1-dichloromethyl-2-chloromethylbenzene (TCOX) is hydrolyzed at room temperature, and the yield and purity are well converted to 2-chloromethyl. Benzoaldehyde (2CMAD) (first embodiment). The preferred range of the concentration of 2-chloromethylbenzaldehyde [η 2CMAD ] produced at this time is as described previously. Further, according to the second embodiment and the third embodiment, the 2-chloromethylbenzaldehyde is not decomposed even during storage in a normal production schedule (for example, about 2 days), and can be supplied to the next step. The reaction.
於上述之反應中，不以高收率得到2CMAD時，分離未反應而殘留的TCOX係繁雜，直接得到高濃度的2CMAD者之工業上的優點大。如上述，2CMAD係分解性。因此，可成為經由水的添加及分離等非加熱之溫和條件的操作，進行安定化的處理之實施態樣的意義係大。實現含有2CMAD的高品質原料組成物之大量生產，更有助於消耗能量的減低。 In the above reaction, when 2CMAD is not obtained in a high yield, the TCOX which is left unreacted and separated is complicated, and the industrial advantage of directly obtaining a high concentration of 2CMAD is large. As described above, 2CMAD is decomposable. Therefore, the operation of the non-heating mild condition such as the addition and separation of water can be performed, and the embodiment of the stabilization process is large. The mass production of high-quality raw material compositions containing 2CMAD is more conducive to the reduction of energy consumption.
具體地，未進行上述第2實施態樣及第3實施態樣所示之處理的2-氯甲基苯甲醛，即使藉由第1實施態樣得到高濃度的2CMAD，也在室溫的保存中於48小時以內因自氧化反應而純度降低20%左右。此意味以2-氯甲基苯甲醛作為中間原料的下一步驟之反應，必須沒有時間差地立刻實施，在工業生產中係非常不方便。因反應現場的時 間調整、故障而不得不保存中間體時，更出現純度降低之發生。作為其之對應，在氮氣環境下阻止自氧化反應之方法係有效。然而，以工業的規模完全地隔絕空氣而在氮氣環境下保管者，係必須特別的設備對應，應考慮空氣進入的危險性。如此地，即使無可避免地會與空氣接觸時，上述第2實施態樣及第3實施態樣也有效。依照本實施態樣，2-氯甲基苯甲醛即使在室溫以下的長期間保存中，也不分解，可供應給下一步驟的反應。 Specifically, 2-chloromethylbenzaldehyde which has not been subjected to the above-described second embodiment and the third embodiment is stored at room temperature even if a high concentration of 2CMAD is obtained by the first embodiment. The purity is reduced by about 20% due to the self-oxidation reaction within 48 hours. This means that the reaction of the next step of using 2-chloromethylbenzaldehyde as an intermediate material must be carried out immediately without time difference, which is very inconvenient in industrial production. Due to the time of the reaction When the intermediate is adjusted and the fault has to be saved, the purity is reduced. As a corresponding, the method of preventing the auto-oxidation reaction under a nitrogen atmosphere is effective. However, those who are completely isolated from the air on an industrial scale and stored in a nitrogen atmosphere must have special equipment correspondence, and the risk of air ingress should be considered. As described above, the second embodiment and the third embodiment are effective even when it is inevitably brought into contact with air. According to this embodiment, 2-chloromethylbenzaldehyde is not decomposed even during storage for a long period of time at room temperature or lower, and can be supplied to the reaction in the next step.
如上述所得的含2-氯甲基苯甲醛之組成物係可使用作為農藥、醫藥、卟啉等之工業材料等的原料，藉由使用本組成物，可實現比習知法短的步驟之製造途徑。依照本發明，如上述地，由於可以高濃度且較佳地安定化得到上述液組成物中的2CMAD，故可高品質且便宜地製造上述化學製品。 As the raw material containing 2-chloromethylbenzaldehyde obtained as described above, a raw material such as an industrial material such as a pesticide, a medicine, or a porphyrin can be used, and by using the composition, a step shorter than the conventional method can be realized. Manufacturing route. According to the present invention, as described above, since the 2CMAD in the liquid composition can be obtained at a high concentration and preferably stabilized, the above chemical product can be produced with high quality and at low cost.
以下，藉由實施例來更詳細說明本發明，惟本發明不是限定於此而解釋者。 Hereinafter, the present invention will be described in more detail by way of examples, but the invention is not limited thereto.
按照情況而定，以水稀釋96重量%濃度之硫酸，調製下表1中記載之濃度的硫酸。其中，添加1-二氯甲基-2-氯甲基苯，一邊保持15-25℃之溫度，一邊攪拌指定時 間。然後，以0.5重量倍(體積約0.4倍量)(對TCOX)之水來稀釋。稀釋混合液係分離成有機相與水相，分離取得此有機相，得到目的之液組成物。以氣相層析術分析構成此有機相的液體組成物，以下顯示結果。下表1中，所得之液組成物中的2CMAD之含有比率[η2CMAD]，係可當作將2CMAD的生成量%[%2CMAD]除以原料TCOX的殘存率%[%TCOX]與2CMAD的生成量%[%2CMAD]之和而得之比率([%2CMAD]/([%2CMAD]+[%TCOX]))，進行評價。 As the case may be, sulfuric acid having a concentration of 96% by weight was diluted with water to prepare sulfuric acid having the concentration described in Table 1 below. Among them, 1-dichloromethyl-2-chloromethylbenzene was added, and the mixture was stirred for a predetermined period while maintaining the temperature at 15 to 25 °C. Then, it was diluted with 0.5 weight (volume about 0.4 times) (for TCOX) water. The diluted mixed liquid is separated into an organic phase and an aqueous phase, and the organic phase is separated to obtain a desired liquid composition. The liquid composition constituting the organic phase was analyzed by gas chromatography, and the results are shown below. In Table 1 below, the content ratio of 2CMAD in the obtained liquid composition [η 2CMAD ] can be regarded as the % of production of 2CMAD [% 2CMAD ] divided by the residual ratio of the raw material TCOX % [% TCOX ] and 2CMAD generation amount% [% 2CMAD] and derived from the ratio of ([% 2CMAD] / ([ % 2CMAD] + [% TCOX])), and evaluated.
由以上之結果可知，依照本發明，以TCOX作為原料，可以高收率得到2CMAD，可以得到高濃度的含2CMAD之液組成物(參照實施例1-1~1-5)。再者，對於TCOX ，水的絕對量即使不足以水解，但當硫酸濃度高時，於指定的反應時間後，以水稀釋時，也顯示水解立刻進行(參照實施例1-1)。相反地，可知即使水的絕對量充分，但當硫酸濃度過少時，即使在反應時及後處理時之任一者中，TCOX也不水解而殘留著(參照比較例1-1、1-2)。 From the above results, according to the present invention, 2CMAD can be obtained in a high yield using TCOX as a raw material, and a liquid composition containing 2CMAD at a high concentration can be obtained (see Examples 1-1 to 1-5). Furthermore, for TCOX When the absolute amount of water is not sufficiently hydrolyzed, when the sulfuric acid concentration is high, the hydrolysis is immediately performed after dilution with water after the specified reaction time (see Example 1-1). On the other hand, even if the absolute amount of water is sufficient, when the sulfuric acid concentration is too small, TCOX does not hydrolyze and remains in any of the reaction and post-treatment (refer to Comparative Examples 1-1 and 1-2). ).
於500mL燒瓶中，加入96重量%濃度的硫酸146.1g(1.43mol)與水9.9g(0.55mol)，將溫度冷卻至25℃為止後，添加1-二氯甲基-2-氯甲基苯115.2g(0.55mol)，在25℃攪拌5小時。於所得之混合物中，以將該燒瓶內容物的內溫保持在30℃以下之方式，滴下水48.3g，進行分液處理。以水85.0g來洗淨所得之油層，進行分液處理，而得到2-氯甲基苯甲醛之粗製物83.7g。其pH顯示約1。藉由高速液體層析術絕對校正曲線法，分析該粗製物，結果2-氯甲基苯甲醛的含量為88.7重量%(2CMAD之含有比率[η2CMAD]超過99%)。將此樣品當作A。再者，實施例2係關於2CMAD之調製，相當於實施例1-3，上述係重新說明其內容者。 In a 500 mL flask, 146.1 g (1.43 mol) of 96% by weight sulfuric acid and 9.9 g (0.55 mol) of water were added, and after cooling to 25 ° C, 1-dichloromethyl-2-chloromethylbenzene was added. 115.2 g (0.55 mol) was stirred at 25 ° C for 5 hours. In the obtained mixture, 48.3 g of water was dropped so that the internal temperature of the contents of the flask was kept below 30 ° C, and liquid separation treatment was performed. The obtained oil layer was washed with water (85.0 g), and subjected to liquid separation treatment to obtain 83.7 g of a crude product of 2-chloromethylbenzaldehyde. Its pH shows about 1. The crude product was analyzed by a high-speed liquid chromatography absolute calibration curve method, and the content of 2-chloromethylbenzaldehyde was 88.7% by weight (the content ratio of 2CMAD [η 2CMAD ] exceeded 99%). Treat this sample as A. Further, the second embodiment relates to the modulation of 2CMAD, and corresponds to the embodiment 1-3, and the above description is repeated.
收率：87.3%(1-二氯甲基-2-氯甲基苯基準) Yield: 87.3% (1-dichloromethyl-2-chloromethylbenzene standard)
GC-MS：m/z118(基峰)，118、154(M+)、156(M++2) GC-MS: m/z 118 (base peak), 118, 154 (M + ), 156 (M + + 2)
藉由與上述樣品A之調製同樣的方法，合成2-氯甲基苯甲醛，於其中添加100ppm的2,6-雙(1,1-二甲基乙 基)-4-甲基苯酚(簡稱BHT)。其pH約1。將此樣品當作B。 2-Chloromethylbenzaldehyde was synthesized by the same method as the preparation of Sample A described above, and 100 ppm of 2,6-bis(1,1-dimethyl B) was added thereto. Base) 4-methylphenol (abbreviated as BHT). Its pH is about 1. Treat this sample as B.
重複前述樣品A之調製步驟，合成2-氯甲基苯甲醛，用10重量%磷酸氫二鈉水溶液83.7g調整至pH=6~8，進行分液處理後，添加BHT 0.008g(相對於2-氯甲基苯甲醛之粗製物而言為100ppm)。將此樣品當作C。 The preparation step of the sample A was repeated to synthesize 2-chloromethylbenzaldehyde, and adjusted to pH=6-8 with 83.7 g of a 10% by weight aqueous solution of disodium hydrogen phosphate. After liquid separation treatment, BHT 0.008 g (relative to 2) was added. - chloromethyl benzaldehyde is 100 ppm as a crude product. Treat this sample as C.
改變氧之有無、安定劑之有無，將樣品A、B、C之各自，觀察在20℃的時間經過。 Each of the samples A, B, and C was observed to pass at a temperature of 20 ° C by changing the presence or absence of oxygen and the presence or absence of a stabilizer.
分析值為HPLC全面積% Analytical value is the full area of HPLC
尚且，在空氣中BHT為500ppm的樣品之安定性結果係與100ppm沒有不同。 Also, the stability of the sample having a BHT of 500 ppm in air was not different from 100 ppm.
由表2之結果可知，使用特定的安定劑者(樣品B)，係即使在空氣保存下也顯示高的安定性，為工業上有用的高純度液組成物。 As is clear from the results of Table 2, the use of a specific stabilizer (Sample B) is a high-purity liquid composition which is industrially useful even when it exhibits high stability even under air storage.
為了確認pH之影響，將加有BHT 100ppm之試料在氮氣環境下保存。下述表3中顯示結果。 In order to confirm the influence of pH, a sample to which BHT 100 ppm was added was stored under a nitrogen atmosphere. The results are shown in Table 3 below.
由上述表3的結果可知，已將pH調整至中性範圍的液組成物，係其保存安定性更高。再者，pH係使用Nikko-Hansen株式會社製pH計EcoScan pH5，在室溫(約25℃)測定者。 From the results of the above Table 3, it is understood that the liquid composition having the pH adjusted to the neutral range is more stable in storage stability. Further, the pH was measured at room temperature (about 25 ° C) using a pH meter EcoScan pH 5 manufactured by Nikko-Hansen Co., Ltd.
已知2-氯苯甲醛係適用作為醫藥及電子材料之中間體。本發明係可作為2-氯苯甲醛化合物之新製造方法等，在產業上利用。 2-Chlorobenzaldehyde is known to be useful as an intermediate in pharmaceuticals and electronic materials. The present invention can be utilized industrially as a new production method of a 2-chlorobenzaldehyde compound.
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| JP2011141552A JP5789430B2 (en) | 2011-06-27 | 2011-06-27 | Method for producing 2-chloromethylbenzaldehyde, 2-chloromethylbenzaldehyde-containing composition and storage method thereof |
| JP2011-141552 | 2011-06-27 |
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|---|---|
| TW201319029A TW201319029A (en) | 2013-05-16 |
| TWI610912B true TWI610912B (en) | 2018-01-11 |
Family
ID=47424156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101122982A TWI610912B (en) | 2011-06-27 | 2012-06-27 | Method for producing 2-chloromethylbenzaldehyde, 2-chloromethylbenzaldehyde-containing composition, and method for storing same |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9029606B2 (en) |
| EP (1) | EP2727901B1 (en) |
| JP (1) | JP5789430B2 (en) |
| KR (1) | KR101940350B1 (en) |
| CN (1) | CN103649034B (en) |
| AU (2) | AU2012276723B2 (en) |
| IL (1) | IL230116A (en) |
| TW (1) | TWI610912B (en) |
| WO (1) | WO2013002265A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3624157A (en) * | 1969-12-17 | 1971-11-30 | Velsicol Chemical Corp | Process for preparing ortho-chlorobenzaldehyde |
| US4546205A (en) * | 1982-06-16 | 1985-10-08 | Pennwalt Corporation | Stabilization of aldehydes |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3499934A (en) * | 1967-02-01 | 1970-03-10 | Diamond Shamrock Corp | Trihalo triformyl benzenes |
| DE3142856A1 (en) * | 1981-10-29 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING 2,4-DICHLOR-5-FLUOR-BENZOYL CHLORIDE |
| DE3669874D1 (en) | 1985-08-29 | 1990-05-03 | Hoechst Ag | 3-DESMETHYL MEVALONIC ACID DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS BASED ON THESE COMPOUNDS, THEIR USE AND INTERMEDIATE PRODUCTS. |
| US5278152A (en) | 1989-12-21 | 1994-01-11 | Hoechst Aktiengesellschaft | 2-formylbenzylphosphonic acid derivatives useful for the treatment of diseases caused by viruses |
| DE3942318A1 (en) * | 1989-12-21 | 1991-06-27 | Hoechst Ag | 2-FORMYLBENZYLPHOSPHONIC ACID DERIVATIVES, THEIR PRODUCTION AND THE USE THEREOF FOR THE TREATMENT OF DISEASES CAUSED BY VIRUSES |
| DE4203792A1 (en) * | 1992-02-10 | 1993-08-12 | Bayer Ag | IMPROVED METHOD FOR PRODUCING OPTIONALLY SUBSTITUTED BENZALDEHYDES |
| JPH0892148A (en) * | 1994-09-26 | 1996-04-09 | Ihara Chem Ind Co Ltd | Method for preventing dehalogenation in producing fluorinated benzaldehydes |
| JP2006335737A (en) * | 2005-06-03 | 2006-12-14 | Ihara Nikkei Kagaku Kogyo Kk | METHOD FOR PRODUCING BENZO[c]HETEROCYCLIC 5-MEMBERED RING COMPOUND |
| JP4162246B2 (en) * | 2005-08-12 | 2008-10-08 | 石原薬品株式会社 | Cyanide-free silver-based plating bath, plated body and plating method |
| JP4901181B2 (en) * | 2005-10-28 | 2012-03-21 | 石原薬品株式会社 | Electroless tin plating bath |
| JP5894026B2 (en) * | 2012-06-29 | 2016-03-23 | ニチコン株式会社 | Method for manufacturing acoustic electrolytic capacitor |
-
2011
- 2011-06-27 JP JP2011141552A patent/JP5789430B2/en active Active
-
2012
- 2012-06-27 EP EP12803767.8A patent/EP2727901B1/en active Active
- 2012-06-27 WO PCT/JP2012/066402 patent/WO2013002265A1/en active Application Filing
- 2012-06-27 TW TW101122982A patent/TWI610912B/en not_active IP Right Cessation
- 2012-06-27 CN CN201280032170.7A patent/CN103649034B/en active Active
- 2012-06-27 US US14/128,239 patent/US9029606B2/en not_active Expired - Fee Related
- 2012-06-27 AU AU2012276723A patent/AU2012276723B2/en not_active Ceased
- 2012-06-27 KR KR1020147000848A patent/KR101940350B1/en active IP Right Grant
-
2013
- 2013-12-23 IL IL230116A patent/IL230116A/en active IP Right Grant
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2016
- 2016-05-27 AU AU2016203505A patent/AU2016203505B2/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3624157A (en) * | 1969-12-17 | 1971-11-30 | Velsicol Chemical Corp | Process for preparing ortho-chlorobenzaldehyde |
| US4546205A (en) * | 1982-06-16 | 1985-10-08 | Pennwalt Corporation | Stabilization of aldehydes |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2727901B1 (en) | 2019-07-31 |
| CN103649034A (en) | 2014-03-19 |
| KR101940350B1 (en) | 2019-01-18 |
| AU2016203505B2 (en) | 2017-08-10 |
| JP2013006807A (en) | 2013-01-10 |
| IL230116A (en) | 2016-03-31 |
| AU2012276723B2 (en) | 2016-06-30 |
| US9029606B2 (en) | 2015-05-12 |
| US20140187822A1 (en) | 2014-07-03 |
| AU2012276723A1 (en) | 2014-01-30 |
| AU2016203505A1 (en) | 2016-06-16 |
| JP5789430B2 (en) | 2015-10-07 |
| KR20140041726A (en) | 2014-04-04 |
| CN103649034B (en) | 2015-11-25 |
| EP2727901A4 (en) | 2015-03-18 |
| WO2013002265A1 (en) | 2013-01-03 |
| EP2727901A1 (en) | 2014-05-07 |
| TW201319029A (en) | 2013-05-16 |
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